Driving the Therapeutic Drug Revolution

Professor Adam McCluskey has been a driving force behind the establishment of the Centre for Kinomics, a world-first research facility.

McCluskey has established the Centre in collaboration with respected neurobiologist Professor Phil Robinson, of the Children's Medical Research Institute (CMRI) at Westmead.

The Centre is named for a biological process called phosphorylation that is mediated by kinases, hence 'kinomics', and which controls the activation of many signalling and enzymatic proteins.

The Centre, which has laboratories at the University of Newcastle and CMRI, has been funded by a $1 million prize from the Ramaciotti Foundation and a $3.1 million grant from the Australian Cancer Research Foundation for the study of protein kinases and the drugs that target them.

The Centre's focus is designing next­ generation drugs for epilepsy, cancer and neuropathic pain. So far the focus has been epilepsy, a disorder where one in three sufferers gain no relief from existing treatments. The goal is creating drugs that do not have the often­ debilitating side effects.

The emerging field revolves around the 518 protein kinases in the body, which are the key signalling proteins behind biological functions. If they malfunction then the body malfunctions.

Pharmaceutical companies invest billions of dollars in research to develop kinase inhibitors.

"It's a crude analogy," says McCluskey, "but in drug design there is the lock and the key. You either want to lock or unlock the protein action and the drug is the key that will enable you to do that."

Using unique equipment costing hundreds of thousands of dollars, the researchers are able to quickly pinpoint the undesirable elements of existing therapeutic drugs.

"We can identify the range of proteins a drug interacts with and look out for red flags," explains McCluskey, a chemist. "There are some proteins you would never want a drug to touch because of the serious, even deadly, side effects."

The Centre is extending a 2007 discovery by a private German drug company that involves a new technique for analysing interactions between kinase inhibitors and hundreds of proteins at a time. The technology is known as Kinobeads and it fast tracks what has been until now a time-consuming process.

Mass spectrometry determines what proteins have been singled out by the Kinobeads, indicating which kinases have remained bound to the drug in question. The process would normally take at least six months but the Centre's cutting-edge technology will reduce it to a few days.

There are 23 research groups around the world waiting for the Centre to produce its first batch of beads. This technology gives us the ability to rapidly enhance our potential to test and manufacture pharmaceuticals that will benefit many individuals suffering from a range of disorders.

Professor McCluskey's research is conducted in collaboration with the Hunter Medical Research Institute's (HMRI) Cancer Research Program. His research is supported by grants from HMRI.

Career Summary

Biography

I am a (BScHons and PhD) graduate in chemistry of the University of Strathclyde, Scotland.

Principle Roles at UON

I am a teaching and research active academic who believes that nurturing students and introducing a positive research experience is one of the pillars of teaching at the University of Newcastle.

Research ExpertiseMy primary area of resaerch is in the medicinal chemistry / chemical biology space where my main focus is in the development of tool compounds, and drugs, targeting endocytosis. The potential outcomes of our research include (but are not limited to) the development of new synthetic methodologies; the development of new drugs & the development of new tools for dissecting signal transduction pathways.

This led to the establishment of the dynamin modulators platform of which I am team leader (chemistry). This team interacts with, and supplies the only known endocytosis inhibitors to research teams worldwide (UK, USA, Germany, Denmark etc). I am also an integral component of the development of new anti-epileptic drugs alongside the National Institute of Health, National Institute of Neurological Disorders and Stroke (Bethesda USA).

I head the chemistry component of the Australian Cancer Research Foundation (supported by Ramaciotti) Centre for Kinomics (CFK), a new approach for direct profiling of cellular kinases, a multi-million dollar initiative providing a unique service to multiple research teams throughout Australia. Kinases are the cancer drug target of the 21st century. The CFK offers a unique opportunity to profile biological probes (drugs) and cellular kinases to identify new therapeutic targets, new uses for old drugs and rapid IC50 determination of individual compounds against the entire cellular kinome (cellular complement of protein kinases). The CFK at the University of Newcastle has established one of the first fully equipped flow chemistry laboratories in Australia.

Qualifications

PhD, University of Strathclyde

Bachelor of Science (Honours), University of Strathclyde

Keywords

Anti-cancer agents

Chemical Biology

Clathrin Inhibitors

Drug Design and Discovery

Dynamin GTPase

Flow Chemistry

Organic Chemistry

Fields of Research

Code

Description

Percentage

030401

Biologically Active Molecules

60

030503

Organic Chemical Synthesis

40

Professional Experience

UON Appointment

Title

Organisation / Department

Professor

University of NewcastleSchool of Environmental and Life SciencesAustralia

Academic appointment

Dates

Title

Organisation / Department

1/01/2010 -

Honorary Scientist

Chemical Biology

The University of SydneyChildren's Medical Research InstituteAustralia

Research Collaborations

The map is a representation of a researchers co-authorship with collaborators across the globe. The map displays the number of publications against a country, where there is at least one co-author based in that country. Data is sourced from the University of Newcastle research publication management system (NURO) and may not fully represent the authors complete body of work.

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